Clinical features and gene mutation detection of essential thrombocythemia and early primary myelofibrosis
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摘要: 目的 探讨原发性血小板增多症(ET)与早期原发性骨髓纤维化(pre-PMF)患者的骨髓病理学、临床特征、血液学参数及基因突变，以期指导治疗，改善预后。方法 按照WHO 2016年标准重新评估ET的诊断，并对其临床特征和相关基因检测进行分析。结果 原诊断的ET患者有78例，24例(31%)患者被重新诊断为pre-PMF，54例(69%)为ET。与ET患者比较，pre-PMF患者发病年龄较大(P=0.001)、白细胞计数较高(P=0.001)、血小板计数较高(P=0.030)、乳酸脱氢酶水平较高(P=0.004)，血红蛋白较低(P=0.001)。pre-PMF患者血栓事件发生率较ET患者高(P=0.014)，二者脾大及性别分布差异均无统计学意义(P=0.389，P=0.307)。2组间及组内比较JAK2V617F、CALR、MPL基因突变负荷分布差异均无统计学意义。共对43例患者进行二代测序，有14例(33%)检测出基因突变，其中pre-PMF 8例(57%)，ASXL1突变3例，EZH2突变2例，SRSF2突变1例，U2AF1突变1例，SF3B1突变1例，TET2突变1例，TP53突变1例，其中有1例同时合并ASXL1、EZH2、TET2突变；ET 6例(43%)，其中U2AF1突变2例，SRSF2突变1例，TET2突变2例，SETBP1突变1例，未同时存在2种或以上的高危分子突变，pre-PMF患者高危分子突变数量较ET更多(P=0.033)。结论 本研究表明可结合骨髓病理学、临床特征、血液学参数及基因突变有助于ET与pre-PMF的鉴别。
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关键词:
- 原发性血小板增多症 /
- 早期原发性骨髓纤维化 /
- 临床特征 /
- 血液学参数 /
- 基因突变
Abstract: Objective To investigate the bone marrow pathology, clinical features, hematological parameters and gene mutations of patients with essential thrombocythemia(ET) and early primary myelofibrosis(pre-PMF), thereby guiding treatment and improving prognosis.Methods The diagnosis of ET was reassessed according to the WHO 2016 criteria, and its clinical features and related genetic tests were analyzed.Results There were 78 patients with originally diagnosed ET, 24 patients(31%) were re-diagnosed as pre-PMF, and 54 patients(69%) were ET. Compared with ET patients, pre-PMF patients were older at onset(P=0.001), had higher white blood cell counts(P=0.001), higher platelet counts(P=0.030), and higher lactate dehydrogenase levels(P=0.004) and lower hemoglobin(P=0.001). The incidence of thrombotic events in pre-PMF was higher than in ET(P=0.014), and there was no significant difference in splenomegaly and gender distribution between the two groups(P=0.389, P=0.307). There was no significant difference in the distribution of JAK2V617F, CALR and MPL gene mutation load between the two groups and within the group. A total of 43 patients underwent next-generation sequencing, and 14 patients(33%) were detected with gene mutations, 8 patients(57%) were pre-PMF, including 3 patients with ASXL1 mutation, 2 patients with EZH2 mutation, 1 patient with SRSF2 mutation, 1 patient with U2AF1 mutation, 1 case with SF3B1 mutation, 1 case with TET2 mutation, 1 case with TP53 mutation, 1 case combined with ASXL1, EZH2 and TET2 mutation. Six cases(43%) were ET, including 2 cases of U2AF1 mutation, 1 case of SRSF2 mutation, 2 cases of TET2 mutation and 1 case of SETBP1 mutation. Two or more coexisting high-risk molecular mutations (HMR) were undetected. The number of HMR in pre-PMF patients was higher than in ET(P=0.033).Conclusion This study shows that the combination of bone marrow pathology, clinical features, hematological parameters and gene mutation can help to differentiate ET from pre-PMF. -
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表 1 pre-PMF与ET患者的临床特征比较
变量 pre-PMF(n=24) ET(n=54) t/z/χ2 P 男∶女/例 9∶15 27∶27 1.045 0.307 发病年龄/岁 71(49~92) 60(26~83) 3.633 0.001 白细胞计数/(×109·L-1) 14.86(8.99，21.27) 9.58(6.95，12.37) 3.183 0.001 血红蛋白/(g·L-1) 121±32 141±22 3.302 0.001 血小板计数/(×109·L-1) 887(607，1291) 703(572，835) 2.176 0.030 乳酸脱氢酶/(U·L-1) 332(243，441) 246(212，284) 2.858 0.004 血栓史/例(%) 6.019 0.014 有 17(71) 22(41) 无 7(29) 32(59) 脾大/例(%) 0.743 0.389 有 6(25) 9(17) 无 18(75) 45(83) 纤维化分级/例(%) 48.092 < 0.001 0级 5(21) 52(96) 1级 19(79) 2(4) 
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表 2 pre-PMF与ET患者的基因突变比较
基因突变负荷 pre-PMF ET t/z P JAK2V617F/% 41.07±18.16 29.17(17.60，40.85) 1.940 0.052 CALR exon9/% 19.33±12.73 20.57±8.40 0.514 0.848 MPL W515K/L/% - 29.79±2.67 F/H 2.814 4.407 - - P 0.084 0.110
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